Biomedical subjects

Alexandra M Levine

Publications and source records attributed to Alexandra M Levine.

At least 37 records · Page 2Linked to original sources

PubMed2005

Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results.

CONTEXT: Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA. OBJECTIVE: To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results. DESIGN, SETTING, AND PATIENTS: Participants were HIV-seropositive (n = 855; mean age, 36 years) and HIV-seronegative (n = 343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women's Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years. MAIN OUTCOME MEASURE: The cumulative incidence of any SIL and high-grade SIL or cancer (HSIL+) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count. RESULTS: Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/microL, 9% (95% CI, 1%-18%); with CD4 counts between 200/muL and 500/microL, 9% (95% CI, 4%-13%); and with CD4 counts greater than 500/microL, 4% (95% CI, 1%-7%). The CIs for these estimates overlapped with those for HIV-seronegative women with normal baseline cytology who were HPV-negative (3%; 95% CI, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSIL+ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIV-seropositive women with CD4 counts greater than 500/microL (hazard ratio [HR], 1.2; 95% CI, 0.5-3.0), but not those with CD4 counts less than or equal to 500/microL (HR, 2.9; 95% CI, 1.2-7.1), was similar to that in HIV-seronegative women. CONCLUSION: The similar low cumulative incidence of any SIL among HIV-seronegative and HIV-seropositive women with CD4 counts greater than 500/microL and who had normal cervical cytology and HPV-negative test results suggests that similar cervical cancer screening practices may be applicable to both groups, although this strategy warrants evaluation in an appropriate clinical trial.

Adult↗

PubMed2005

Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women.

BACKGROUND: Whether the natural history of human papillomavirus (HPV) infection is affected by bacterial vaginosis (BV) or Trichomonas vaginalis (TV) infection has not been adequately investigated in prospective studies. METHODS: Human immunodeficiency virus 1 (HIV-1)-infected (n=1763) and high-risk HIV-1-uninfected (n=493) women were assessed semiannually for BV (by Nugent's criteria), TV infection (by wet mount), type-specific HPV (by polymerase chain reaction with MY09/MY11/HMB01 HPV primers), and squamous intraepithelial lesions (SIL) (by cytological examination). Sexual history was obtained from patient report at each visit. Risk factors for prevalent and incident HPV infection and SIL were evaluated by use of multivariate models. RESULTS: BV was associated with both prevalent and incident HPV infection but not with duration of HPV infection or incidence of SIL. TV infection was associated with incident HPV infection and with decreased duration and lower prevalence of HPV infection. TV infection had no association with development of SIL. Effects of BV and TV infection were similar in HIV-1-infected and high-risk HIV-1-uninfected women. HIV-1 infection and low CD4(+) lymphocyte count were strongly associated with HPV infection and development of SIL. CONCLUSIONS: BV and TV infection may increase the risk of acquisition (or reactivation) of HPV infection, as is consistent with hypotheses that the local cervicovaginal milieu plays a role in susceptibility to HPV infection. The finding that BV did not affect persistence of HPV infection and that TV infection may shorten the duration of HPV infection helps explain the lack of effect that BV and TV infection have on development of SIL.

Adult↗

PubMed2005

Weekly docetaxel is safe and effective in the treatment of advanced-stage acquired immunodeficiency syndrome-related Kaposi sarcoma.

BACKGROUND: Intravenous paclitaxel, 100 mg/m(2), given over 3 hours every 2 weeks is associated with a response rate of 59% in patients with recurrent or refractory acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS). However, this regimen is associated with significant myelosuppression, and the inconvenience of a 3-hour infusion. Moreover, no effective therapies have been defined for use after treatment failure with this agent. A Phase II trial was conducted with weekly docetaxel in patients with advanced-stage KS to assess safety and antitumor activity. METHODS: Docetaxel was administered at a dose of 25 mg/m(2) intravenously over 15-30 minutes weekly for 8 weeks. Thereafter, if the patient experienced stable disease or better response, treatment doses were given every other week until complete disease remission, disease progression, or unacceptable toxicity occurred. RESULTS: Twelve patients were accrued-9 had > 25 mucocutaneous lesions, 1 had lymphedema, and 2 had visceral involvement. Ten patients (83%) had previous systemic chemotherapy, including 4 who received previous paclitaxel. Treatment was well tolerated, with no Grade 4 toxicity of any type. Grade 3 neutropenia occurred in 33% of patients but no patient had neutropenic fever. Five patients (42%) achieved a partial response, including 1 who had previously failed to respond to paclitaxel. The median time to disease progression was 26 months (range, 5-53 months). With a median follow-up period of 45 months, the median survival point had not been reached. CONCLUSIONS: Weekly docetaxel is safe, with reasonable antitumor activity in patients with advanced-stage, recurrent, or refractory AIDS-related KS.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Non-AIDS-defining cancers and HIV infection.

With fewer patients now succumbing to infectious complications of AIDS, other HIV-related morbidities, such as malignancies, have become increasingly important. Apart from Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, which are considered as AIDS-defining, several additional cancers, referred to as non-AIDS-defining cancers, are also statistically increased in HIV-infected persons. These include Hodgkin's disease, anal carcinoma, lung cancer, nonmelanomatous skin cancer, and testicular germ cell tumors, among others. However, the types of cancer observed at an increased frequency and the relative risks reported vary widely among studies. Although immunosuppression is consistently associated with an increased risk of AIDS-related malignancies, the role of immunosuppression in the pathogenesis of non-AIDS- defining cancers is controversial. Although data regarding the optimal management of these cancers are lacking, current studies suggest that patients with HIV-associated malignancies should be treated with similar approaches to those of their counterparts in the general population.

Antineoplastic Agents↗

PubMed2005

Non-AIDS-Defining Cancers and HIV Infection.

With fewer patients now succumbing to infectious complications of AIDS, other HIV-related morbidities such as malignancies have become increasingly important. Apart from Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, which are considered as AIDS-defining, several additional cancers, referred to as non-AIDS-defining cancers, are also statistically increased in HIV-infected persons. These include Hodgkin's disease, anal carcinoma, lung cancer, nonmelanomatous skin cancer, and testicular germ cell tumors, among others. However, the types of cancer observed at an increased frequency and the relative risks reported vary widely among studies. Although immunosuppression is consistently associated with an increased risk of AIDS-related malignancies, the role of immunosuppression in the pathogenesis of non-AIDS- defining cancers is controversial. Although data regarding the optimal management of these cancers are lacking, current studies suggest that patients with HIV-associated malignancies should be treated with similar approaches to those of their counterparts in the general population.

Journal Article↗

PubMed2005

Angiogenesis and hematological malignancies.

Since the initial hypotheses on the importance of angiogenesis in the pathogenesis of cancer approximately 30 years ago, there have been major advances in the understanding of the cellular and molecular mechanisms involved in the regulation of this complex process of new vessel formation. Among the multitude of factors, vascular endothelial growth factor (VEGF) has emerged as one of the most potent angiogenic factors, being implicated in the initiation of signal transduction responsible for cell proliferation, survival, migration and adhesion. Inhibition of VEGF and its signaling pathway offers a potential new molecular target in cancer therapy. This article reviews the role of angiogenesis and its mediators, particularly vascular endothelial growth factors, in hematological malignancies, as well as the potential use of anti-angiogenic therapies in the management of these conditions.

Angiogenesis Inducing Agents↗

PubMed2005

Variants of human papillomaviruses 16 and 18 and their natural history in human immunodeficiency virus-positive women.

Highly oncogenic human papillomavirus (HPV) 16 and 18 variants might be expected to be particularly aggressive in HIV-positive women. The association of HPV16 and 18 variant lineages with race, human immunodeficiency virus (HIV) coinfection, CD4+ T-cell count, HIV-RNA level, time-to-clearance of HPV infection and presence of squamous intraepithelial lesions (SIL) among women in the Women's Interagency HIV Study was studied. Subjects were followed semi-annually with Pap smear and cervicovaginal lavage (CVL). HPV DNA was detected in CVLs using MY09/11 L1 PCR assay. Specimens positive for HPV16/18 underwent E6 PCR and sequencing to determine the variant present. Specimens from 195 HPV16- and 162 HPV18-positive women were classified into variant lineages based on sequencing results. African variants of HPV16 and HPV18 were significantly more prevalent among African-Americans than among Caucasians [42 versus 14 % (P=0.001) and 60 versus 13 % (P<0.001), respectively]. However, it was not possible to detect associations between the HPV16 or 18 variant lineages and other factors studied. African variants of HPV16/18 were more common in women of African descent living outside Africa, which could reflect mixing behaviours and/or immunogenetic factors. However, in a large population of HIV-infected women, the variant of HPV16 or 18 was unrelated to persistence of infection or presence of SIL. If non-European variants are more oncogenic, the effect may involve a late stage in cervical tumorigenesis.

AIDS-Related Opportunistic Infections↗

PubMed2004

Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study.

BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.

Adolescent↗

PubMed2004

Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection.

The role of mucosal immunity in human papillomavirus (HPV)-related cervical diseases is poorly understood. To characterize the local immune microenvironment in cervical intraepithelial neoplasia (CIN) 2/3 and determine the effects of HIV infection, we compared samples from three groups: normal cervix, CIN 2/3 from immunocompetent women (HIV- CIN 2/3), and CIN 2/3 from HIV seropositive women (HIV+ CIN 2/3). CIN 2/3 lesions contained increased numbers of immune cells from both the acquired and innate arms of the immune response in stroma [CD4+ and CD8+ T cells, macrophages, mast cells, B cells, neutrophils, and natural killer (NK) cells] and dysplastic epithelium (CD4+ T cells, macrophages, and NK cells). Immune cells in CIN 2/3 expressed activation markers, as measured by interleukin-2 receptor (IL-2R) and transcription factor T bet. Interferon-gamma production was significantly up-regulated in CIN lesions and was expressed by CD4+ and CD8+ T cells and NK cells, indicating the activation of immune cells. Abundant presence of transforming growth factor-beta+ CD25+ cells in the infiltrates associated with CIN lesions, and of immature CD1a+ dendritic cells expressing IL-10 and transforming growth factor-beta, indicate that CIN is associated with an influx of immune cells that produce a mixture of proinflammatory and regulatory cytokines. In HIV+ CIN, immune cell densities (CD4+ T cells, macrophages, neutrophils, and NK cells) and expression of interferon-gamma were significantly decreased compared with HIV- CIN. Regulatory cytokines were also down-regulated in this group. Therefore, both pro- and anti-inflammatory responses present in CIN 2/3 lesions are suppressed in HIV-seropositive women.

Adult↗

PubMed2004

T-cell lymphoma in HIV-infected patients.

Linkage of AIDS and cancer registries has indicated an increase in T-cell lymphomas among individuals infected with the HIV. The characteristics of T-cell versus B-cell lymphoma in HIV-infected patients are not well described. Retrospectively, 11 cases of T-cell lymphoma were identified from the AIDS-Lymphoma Registry at the University of Southern California. These patients were compared with 418 consecutive HIV-seropositive patients with B-cell lymphoma diagnosed and treated within the same time period. T-cell lymphomas comprised 3% of all AIDS lymphomas. Pathologic types included peripheral T-cell lymphoma in 5; anaplastic large cell lymphoma in 3; and angioimmunoblastic, enteropathy type, and human T-cell lymphotropic virus-I-related adult T-cell lymphoma/leukemia in 1 case each. No differences in demographic characteristics, history of prior opportunistic infection, or immunologic characteristics were observed between T-cell and B-cell cases. Extranodal involvement of the skin (36% vs. 2%, P < 0.001) and bone marrow (45% vs. 15%, P = 0.019) was significantly more common in T-cell lymphomas. The median survival of patients with T-cell lymphomas was not significantly different from that of B-cell lymphoma patients (10.6 vs. 6.6 months, P = 0.13). T-cell lymphomas in HIV-infected patients represent a spectrum of pathologic types. T-cell lymphomas differ from B-cell cases in terms of a higher propensity for skin and bone marrow involvement. The median survival of patients with T-cell lymphoma is comparable to that of patients with B-cell AIDS-related lymphoma.

Adult↗

PubMed2004

Cancer risk among participants in the women's interagency HIV study.

BACKGROUND: The HIV epidemic has been associated with an increased incidence of specific cancers. However, less is known about cancers occurring in HIV-infected women than men. METHODS: To determine the risk of cancer among HIV-infected and at-risk HIV-uninfected women, cancer incidence data from the Women's Interagency HIV Study (WIHS) were compared with data from the population-based United States Surveillance, Epidemiology, and End Results (SEER) registry. Age- and race-adjusted standardized incidence ratios (SIRs) were computed and exact statistical tests were used to measure significance. RESULTS: Among the 1950 women participants (1554 HIV infected, 391 HIV uninfected, and 5 HIV seroconverters), 48 cancers were diagnosed during study follow-up. Among HIV-infected women, significantly (P < 0.05) increased incidence rates were observed for all cancer types (SIR = 1.9), Kaposi sarcoma (SIR = 213.5), non-Hodgkin lymphoma (NHL) (SIR = 19.0), and lung cancer (SIR = 6.3) when compared with SEER rates. Lung cancer incidence was also elevated (P = 0.07) among the HIV-uninfected women (SIR = 6.9), when compared with SEER rates, and was similar to the SIR for HIV-infected women. While the incidence rate of NHL among HIV-infected women was significantly lower during the era of highly active antiretroviral therapy (HAART) compared with the pre-HAART era (relative risk = 0.15, P = 0.005), the incidence of NHL among HIV-infected WIHS participants remained significantly higher than in the US population (SIR = 6.4, 95% CI = 1.3-15.5). CONCLUSION: In the HAART era, the higher rates of cancer among HIV-infected women, coupled with increased life expectancy, should lead to more intensive cancer screening and prevention efforts in this population.

Adult↗

PubMed2004

Highly active antiretroviral therapy and cervical squamous intraepithelial lesions in human immunodeficiency virus-positive women.

BACKGROUND: Women infected with human immunodeficiency virus (HIV) have an increased risk of persistent squamous intraepithelial lesions (SILs) of the cervix. We assessed the association between use of highly active antiretroviral therapy (HAART) and regression of SIL in HIV-infected women enrolled in the Women's Interagency HIV Study, a large, multicenter, prospective cohort study. METHODS: Of 2059 HIV-infected participants, 312 HIV-infected women had normal cervical cytology at baseline and were subsequently diagnosed during 7 years of follow-up with incident SIL. Pap smears, CD4+ T-cell counts, and information regarding use of HAART were obtained every 6 months. The outcome of interest was lesion regression, defined as two consecutive normal Pap smears 6 months apart. Incidence rates of SIL regression were computed among person-years at risk, both before and after HAART initiation. All statistical tests were two-sided. RESULTS: Of 312 women, 141 had lesions that regressed to normal cytology, with a median time to regression of 2.7 years. Overall, the incidence of regression increased (P(trend) =.002) over time after HAART was introduced. At incident SIL, median CD4+ T-cell counts were lower in women whose lesions did not regress than in women whose lesions regressed (230 versus 336 cells/microL; P<.01). Before HAART was introduced, the rate of lesion regression was 0.0% (95% confidence interval [CI' = 0.0% to 2.4%). After HAART was introduced, the rate was 12.5% (95% CI = 9.9% to 15.1%) and was related to post-HAART CD4+ T-cell counts (P(trend) =.002). CONCLUSIONS: HAART use was associated with increased regression of SIL among HIV-infected women, and among women who used HAART, increased CD4+ T-cell counts were associated with a greater likelihood of regression. However, the majority of cervical lesions among HIV-infected women, even among individuals who used HAART, did not regress to normal.

AIDS-Related Opportunistic Infections↗

PubMed2004

Liposome-encapsulated doxorubicin in combination with standard agents (cyclophosphamide, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma: results of therapy and correlates of response.

PURPOSE: To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome. PATIENTS AND METHODS: Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m(2) was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression. RESULTS: Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm(3) (range, 19/mm(3) to 791/mm(3)). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P =.027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism. CONCLUSION: Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Anemia in HIV infection: clinical impact and evidence-based management strategies.

Anemia in human immunodeficiency virus (HIV)-infected patients can have serious implications, which vary from functional and quality-of-life decrements to an association with disease progression and decreased survival. In 2002, 16 members of the Anemia in HIV Working Group, an expert panel of physicians involved in the care of HIV-infected patients that met first in 1998, reconvened to assess new data and to translate these data into evidence-based treatment guidelines. The group reached consensus on the prevalence of anemia in the highly active antiretroviral therapy era; the risk factors that are independently associated with the development of anemia; the impact of anemia on quality of life, physical functioning, and survival; the impact of the treatment of hepatitis C virus coinfection on anemia in HIV-infected patients; evidence-based guidelines for treatment of anemia in HIV-infected patients, including the therapeutic role of epoetin alfa; and directions for future research.

Anemia↗

PubMed2004

Phase I studies of interleukin (IL)-2 and rituximab in B-cell non-hodgkin's lymphoma: IL-2 mediated natural killer cell expansion correlations with clinical response.

PURPOSE: Expansion and activation of natural killer (NK) cells with interleukin-2 (IL-2) may enhance antibody-dependent cellular cytotoxicity (ADCC), an important mechanism of rituximab activity. Two parallel Phase I studies evaluated combination therapy with rituximab and IL-2 in relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). EXPERIMENTAL DESIGN: Thirty-four patients with advanced NHL received rituximab (375 mg/m(2) i.v. weekly, weeks 1-4) and escalating doses of s.c. IL-2 [2-7.5 MIU daily (n = 19) or 4.5-14 million international units three times weekly (n = 15), weeks 2-5]. Safety, tolerability, clinical responses, NK cell counts, and ADCC activity were evaluated. RESULTS: Maximally tolerated doses (MTD) of IL-2 were 6 MIU daily and 14 million international units thrice weekly. The most common adverse events were fever, chills, and injection site reactions. Dose-limiting toxicities were fatigue and reversible liver enzyme test elevations. Of the 9 patients enrolled at the daily schedule MTD, 5 showed clinical response. On the thrice-weekly schedule at the MTD, 4 of 5 patients responded. Responders showed median time to progression of 14.9 and 16.1 months, respectively, for the two studies. For the same total weekly dose, thrice-weekly IL-2 administration induced greater increases in NK cell counts than daily dosing, and NK cells correlated with clinical response on the thrice-weekly regimen. ADCC activity was increased and maintained after IL-2 therapy in responding and stable disease patients. CONCLUSIONS: Addition of IL-2 to rituximab therapy is safe and, using thrice-weekly IL-2 dosing, results in NK cell expansion that correlates with response. This combination treatment regimen merits additional evaluation in a randomized clinical trial.

Adult↗

PubMed2004

Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes.

Hepatitis C virus (HCV) is a nonretroviral oncogenic RNA virus, which is frequently associated with hepatocellular carcinoma (HCC) and B cell lymphoma. We demonstrated here that acute and chronic HCV infection caused a 5- to 10-fold increase in mutation frequency in Ig heavy chain, BCL-6, p53, and beta-catenin genes of in vitro HCV-infected B cell lines and HCV-associated peripheral blood mononuclear cells, lymphomas, and HCCs. The nucleotide-substitution pattern of p53 and beta-catenin was different from that of Ig heavy chain in HCV-infected cells, suggesting two different mechanisms of mutation. In addition, the mutated protooncogenes were amplified in HCV-associated lymphomas and HCCs, but not in lymphomas of nonviral origin or HBV-associated HCC. HCV induced error-prone DNA polymerase zeta, polymerase iota, and activation-induced cytidine deaminase, which together, contributed to the enhancement of mutation frequency, as demonstrated by the RNA interference experiments. These results indicate that HCV induces a mutator phenotype and may transform cells by a hit-and-run mechanism. This finding provides a mechanism of oncogenesis for an RNA virus.

B-Lymphocytes↗

PubMed2004

Low incidence of invasive cervical cancer among HIV-infected US women in a prevention program.

OBJECTIVE: To measure the incidence of invasive cervical cancer (ICC) in US women infected with HIV. DESIGN: Multicenter prospective cohort study, conducted between October 1994, and September 2001. SETTING: HIV research centers operating as six urban consortia in the Women's Interagency HIV Study. SUBJECTS: A total of 2131 women (462 HIV seronegative, 1661 HIV seropositive, and eight seroconverters). Women with a history of hysterectomy or of cervical cancer at baseline evaluation were excluded. INTERVENTION: Cervical cytology obtained at 6-month intervals, with a colposcopy referral threshold of atypia, followed by individualized treatment. MAIN OUTCOME MEASURE: ICC diagnoses obtained from study databases and regional cancer registries and confirmed by a gynecologic pathologist. RESULTS: No incident ICC were observed in HIV seronegative women during 2375 woman-years of observation. During 8260 woman-years of observation, eight putative incident cases of cervical cancer were identified in HIV seropositive women, but only one was confirmed, yielding an incidence rate of 1.2/10 000 woman-years (95% confidence interval, 0.3-6.7/10 000 woman-years). The difference in incidence between HIV seropositive and seronegative women was not significant (P = 1.0). CONCLUSION: ICC is uncommon in HIV-infected US women participating in a regular prevention program.

Adult↗

PubMed2004

Effect of antiretroviral therapy on the incidence of genital warts and vulvar neoplasia among women with the human immunodeficiency virus.

OBJECTIVE: The purpose of this study was to determine the incidence and predictors of genital warts and vulvar intraepithelial neoplasia among women with the human immunodeficiency virus. STUDY DESIGN: This was a multicenter prospective cohort study comprised of women without warts or vulvar intraepithelial neoplasia at baseline who underwent CD4 count, human immunodeficiency virus RNA measurement, examination, Papanicolaou test, and biopsy, as indicated, every 6 months. Human papillomavirus DNA typing was examined at baseline. RESULTS: The incidence of warts among women who were human immunodeficiency virus seronegative was 1.31 versus 5.01 per 100 person-years among women who were seropositive (P < .001). Incidence of vulvar intraepithelial neoplasia among women who were seronegative was 1.31 versus 4.67 per 100 person-years among women who were seropositive (P < .001). In multivariable analysis, warts were associated with highly active antiretroviral therapy (relative hazard, 0.76), CD4 count (relative hazard, 0.91/100 cell/cm(2) increase), acquired immunodeficiency syndrome (relative hazard, 1.25), abnormal Papanicolaou test results (relative hazard, 2.18), high- or medium-risk human papillomavirus types (relative hazard, 1.91), low-risk human papillomavirus types (relative hazard, 1.48), smoking (relative hazard, 1.43), having 1 child (relative hazard, 1.54), and age (relative hazard, 0.74/10 years). Vulvar intraepithelial neoplasia was linked to highly active antiretroviral therapy (relative hazard, 0.65), CD4 count (relative hazard, 0.92), abnormal Papanicolaou test results (relative hazard, 16.03), high- or medium-risk human papillomavirus types (relative hazard, 1.37), and age (relative hazard, 0.85/10 years). CONCLUSION: Warts and vulvar intraepithelial neoplasia are common among women with human immunodeficiency virus. Highly active antiretroviral therapy decreases their incidence.

Adult↗